Remarkable progress has been made over the past five years in isolation and characterization of messenger RNAs from eucaryotic cells. However, the mechanism by which the biosynthesis of such messengers is regulated remains obscure. In order to approach this question we propose to study the in vitro synthesis of histone mRNA and viral mRNA representing the integrated adenovirus-2 genome from chromatin. The synthesis of such RNA molecules will be quantitated by appropriate DNA/RNA hybridization. The features of chromosome structure which promote or limit transcription will be elucidated by removal of specific nuclear proteins, mixing experiments and chromatin reconstitution. In addition, the same basic methodology will be used to determine what precludes transcription of satellite DNA sequences in chromatin. The location and organization of histone genes in the chromosomes will be studied by fractionating chromatin from HeLa cells in various phases of the cell-cycle and from other cells inactive in histone biosynthesis. BIBLIOGRAPHIC REFERENCES: Martinson, H.M. and McCarthy, B.J. (1975). Histone-histone associations within chromatin. Crosslinking studies using tetranitromethane. Biochemistry 14, 1073. Polisky, B. and McCarthy, B.J. (1975). Location of histones on SV40 DNA. Proc. Nat. Acad. Sci. USA, in press (August issue).